Mask set for microarray, method of fabricating mask set, and method of fabricating microarray using mask set

ABSTRACT

A mask set with a light-transmitting region of a controlled size includes a plurality of masks for performing in-situ synthesis on probes of a microarray, wherein each mask includes a light-transmitting region and a light-blocking region, and the size of the light-transmitting region is equal to or greater than about 5% of the total size of the light-transmitting and light-blocking regions.

This application claims priority from Korean Patent Application No.10-2007-0014896 filed on Feb. 13, 2007 in the Korean IntellectualProperty Office, the contents of which are herein incorporated byreference in their entirety.

BACKGROUND OF THE INVENTION

1. Technical Field

The present disclosure is directed to a mask set, and more particularly,to a mask set for in-situ synthesizing probes of a microarray, a methodof fabricating the mask set, and a method of fabricating the microarrayusing the mask set.

2. Description of the Related Art

Advances in the genome project have revealed genome nucleotide sequencesof various organisms. Accordingly, there is a growing interest inmicroarrays. Microarrays are widely used for gene expression profiling,genotyping, detection of mutations and polymorphisms, such as singlenucleotide polymorphisms (SNPs), analysis of proteins and peptides,screening of potential medicine, development and production of newmedicine, and the like.

A microarray includes a plurality of probes fixed to a substrate. Theprobes may be directly fixed to the substrate by spotting or in-situsynthesized using photolithography and then fixed to the substrate. Inparticular, in-situ synthesis using photolithography is recently drawingattention because it facilitates mass production of microarrays.

A plurality of masks are used for the in-situ synthesis of probes. Eachmask includes light-transmitting regions and light-blocking regions. Inaddition, each mask is allocated any one of a plurality of, e.g., four,probe monomers. If there are four probe monomers, a maximum of fourseparate masks are required to complete a monomer layer of a probe. If aprobe is composed of 25 monomer layers, a maximum of 100 separate maskswould be required.

The light-transmitting regions of each mask respectively correspond toprobe cells where monomers are to be synthesized. Therefore, the patternof each mask varies according to the sequence of target probes that areto be synthesized in each probe cell. That is, while light-transmittingregions may occupy an average of, for example, 25% of an entire mask,their proportion in each mask may be far smaller than the averageaccording to the probe sequence of each probe cell. In the extreme case,some masks may have light-transmitting regions which occupy less than 1%thereof. If a proportion of the light-transmitting regions in some masksis excessively small, it is challenging to perform precise patterningduring mask fabrication. For example, since the light-transmittingregions are either partially open or closed, light-transmitting regionsof a desired size and/or shape cannot be secured. This situationaggravates as microarrays become more integrated.

SUMMARY OF THE INVENTION

Embodiments of the present invention provide a mask set with acontrolled proportion of light-transmitting regions.

Embodiments of the present invention also provide a mask layoutdetermination system controlling the proportion of light-transmittingregions of a mask layout.

Embodiments of the present invention also provide a mask layoutdetermination method which controls a proportion of light-transmittingregions of a mask layout.

Embodiments of the present invention also provide a method offabricating a mask set using each mask layout with a controlledproportion of light-transmitting regions.

Embodiments of the present invention also provide a method offabricating a microarray using the mask set.

However, the features of the embodiments of the present invention arenot restricted to the one set forth herein. The above and other featureswill become more apparent to one of daily skill in the art to whichembodiments of the present invention pertain by referencing a detaileddescription of the present invention given below.

According to an aspect of the present invention, there is provided amask set including a plurality of masks performing in-situ synthesis onprobes of a microarray, wherein each mask includes light-transmittingregions and light-blocking regions, and a proportion of thelight-transmitting regions in each mask is equal to or greater thanabout 5% of a total proportion of the light-transmitting andlight-blocking regions in each mask.

According to another aspect of the present invention, there is provideda mask layout determination system including a pattern determinationunit for allocating light-transmitting regions and light-blockingregions to each of a plurality of mask layouts which perform in-situsynthesis on probes of a microarray; a selection unit for selecting anyone of the mask layouts; a comparison unit for comparing a proportion ofthe light-transmitting regions in a selected mask layout with a minimumlight-transmitting proportion; and a pattern change unit for exchanginga light-blocking region of the selected mask layout with alight-transmitting region of an unselected mask layout if the proportionof the light-transmitting regions in the selected mask layout is smallerthan the minimum light-transmitting proportion.

According to another aspect of the present invention, there is provideda mask layout determination method including allocatinglight-transmitting regions and light-blocking regions to each of aplurality of mask layouts which perform in-situ synthesis on probes of amicroarray; and exchanging a light-blocking region of a mask layout witha light-transmitting region of another mask layout wherein a proportionof the light-transmitting regions in each mask layout is equal to orgreater than a minimum light-transmitting proportion.

According to another aspect of the present invention, there is provideda method of fabricating a mask set. The method includes allocatinglight-transmitting regions and light-blocking regions to each of aplurality of mask layouts which perform in-situ synthesis on probes of amicroarray; exchanging a light-blocking region of a mask layout with alight-transmitting region of another mask layout wherein a proportion ofthe light-transmitting regions in each mask layout is equal to orgreater than a minimum light-transmitting proportion; and fabricating aplurality of masks using the mask layouts which include each mask layoutwhose light-blocking region is exchanged with a light-transmittingregion.

According to another aspect of the present invention, there is provideda method of fabricating a microarray. The method includes providing asubstrate comprising an array of a plurality of probe cells and having asurface protected by a photolabile protecting group; and performingin-situ synthesis on probes of a microarray using a mask set whichcomprises a plurality of masks, each comprising light-transmittingregions and light-blocking regions, wherein a proportion of thelight-transmitting regions is equal to or greater than about 5% of atotal proportion of the light-transmitting and light-blocking regions.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features of embodiments of the present inventionwill become more apparent by describing in detail exemplary embodimentsthereof with reference to the attached drawings.

FIG. 1 is a perspective view of a microarray fabricated according to anembodiment of the present invention.

FIG. 2 is a cross-sectional view of the microarray taken along a lineII-II′ of FIG. 1.

FIG. 3 is a plan view of a mask according to an embodiment of thepresent invention.

FIG. 4 is a cross-sectional view of the mask taken along a line IV-IV′of FIG. 3.

FIGS. 5A through 5C are cross-sectional views for explaining a method offabricating the mask illustrated in FIG. 4.

FIG. 6 is a plan view of a mask according to another embodiment of thepresent invention.

FIG. 7 is a perspective view of a mask set according to an embodiment ofthe present invention.

FIG. 8 is a flowchart illustrating a method of fabricating a mask setaccording to an embodiment of the present invention.

FIG. 9 is a block diagram of a mask layout determination systemaccording to an embodiment of the present invention.

FIG. 10 is a flowchart illustrating a mask layout determination methodaccording to an embodiment of the present invention.

FIGS. 11 through 14 are perspective views for explaining operations ofchanging patterns of mask layouts according to an embodiment of thepresent invention.

FIGS. 15 through 21 are perspective views for explaining a method offabricating a microarray according to an embodiment of the presentinvention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Embodiments of the present invention will now be described more fullywith reference to the accompanying drawings, in which exemplaryembodiments of the invention are shown. The invention may, however, beembodied in many different forms and should not be construed as beinglimited to the embodiments set forth herein. Like reference numerals inthe drawings denote like elements, and thus their description will beomitted.

Hereinafter, embodiments of the present invention will be described indetail with reference to the accompanying drawings.

FIG. 1 is a perspective view of a microarray 100 fabricated according toan embodiment of the present invention. FIG. 2 is a cross-sectional viewof the microarray 100 taken along a line II-II′ of FIG. 1.

Referring to FIGS. 1 and 2, the microarray 100 includes a substrate 110and a plurality of probes 140. The probes 140 are coupled onto thesubstrate 110. The microarray 100 may further include a fixing layer 120and/or a linker 130 between the probes 140 and the substrate 110. Thefixing layer 120 and/or the linker 130 couples the probes 140 to thesubstrate 110.

The substrate 110 may be, for example, a flexible or rigid substrate. Anexample of a flexible substrate includes a membrane or plastic film suchas nylon and nitrocellulose. Examples of a rigid substrate include asilicon substrate and a transparent glass substrate formed of soda limeglass. In the case of the silicon substrate or the transparent glasssubstrate, non-specific binding rarely occurs during hybridization. Inaddition, various thin-film fabrication processes and a photolithographyprocess, which are well established and applied to the process offabricating semiconductor devices or liquid crystal display (LCD)panels, can also be applied to fabricate the silicon substrate or thetransparent glass substrate.

The probes 140 may be, for example, oligomer probes. An oligomer is apolymer composed of two or more covalently bonded monomers, and itsmolecular weight may be approximately 1,000 or less. The oligomer mayinclude approximately 2 through 500 monomers. More specifically, theoligomer may include approximately 5 through 30 monomers. However, theoligomer, which is mentioned in the present invention, is not limited tothe above figures, and it encompasses everything that can be called‘oligomer’ in the art.

Each monomer of an oligomer probe may be, for example, a nucleoside, anucleotide, an amino acid, or a peptide.

Each of the nucleosides and nucleotides may include a methylated purineor pyrimidine and an acylated purine or pyrimidine as well as thewell-known purine and pyrimidine bases. Examples of the purine andpyrimidine bases may include adenine (A), guanine (G), thymine (T),cytosine (C), and uracil (U). In addition, each of the nucleosides andnucleotides may include ribose and deoxyribose sugar, but also modifiedsugar obtained by replacing one or more hydroxyl groups with halogenatoms or aliphatic families or by being bonded to functional groups suchas ether and amine.

The amino acid may be an L-, D-, or nonchiral amino acid found innature, a modified amino acid, or an amino acid analog.

The peptide is a compound created by an amino bond between a carboxylgroup of an amino acid and an amino group of another amino acid.

Therefore, each of the oligomer probes 140 may be formed of two or morenucleocides, nucleotides, amino acids, or peptides.

Each of the probes 140 may be formed by in-situ synthesis of probemonomers. The in-situ synthesis of the probe monomers may be performedusing a mask set which includes a plurality of masks. The masks and themask set will be described in detail later.

The fixing layer 120 interposed between the substrate 110 and the probes140 couples the probes 140 to the substratel 10. The fixing layer 120may be formed of a substantially stable material under a hybridizationanalysis condition, that is, a material which is not hydrolyzed whencontacting phosphate of pH 6-9 or a TRIS buffer. For example, the fixinglayer 120 may be formed of a silicon oxide film such as aplasma-enhanced tetraethyl orthosilicate (PE-TEOS) film, a high densityplasma (HDP) oxide film, a P—SiH₄ oxide film or a thermal oxide film, asilicate such as a hafnium silicate or a zirconium silicate, a metaloxynitride film such as a silicon oxynitride film, a hafnium oxynitride(HfON) film or a zirconium oxynitride film, a metal oxide film such as atitanium oxide film, a tantalum oxide film, an aluminum oxide film, ahafnium oxide film, a zirconium oxide film or an indium tin oxide (ITO)film, metal such as polyimide, polyamine, gold, silver, copper orpalladium, or a polymer such as polystyrene, a polyacrylic acid orpolyvinyl.

The linker 130 may optionally be interposed between the fixing layer 120and the probes 140. The linker 130 couples the probes 140 to the fixinglayer 120. Therefore, the linker 130 may be formed of a materialincluding a functional group which can be coupled to the fixing layer120 and a functional group which can be coupled to the probes 140.Furthermore, the linker 130 may provide a spatial margin forhybridization. To this end, the length of the linker 130 may be, but isnot limited to, about 6 through 50 atoms.

The microarray 100 configured as described above includes a plurality ofprobe cells. For illustrative purposes, an exemplary, non-limitingmicroarray includes first through twelfth probe cells P₁-P₁₂. It is tobe understood that microarrays according to other embodiments can beconfigured with a different number of probe cells. Each of the firstthrough twelfth probe cells P₁-P₁₂ is a segment to which the probes 140are coupled. Therefore, it may be understood that the first throughtwelfth probe cells P₁-P₁₂ include the probes 140 and an object to whichthe probes 140 are coupled. As described above, the object to which theprobes 140 are coupled may be the substrate 110, the fixing layer 120,and/or the linker 130. Therefore, it can be understood that anythingreferred to as a probe cell includes the object and at least one of thesubstrate 110, the fixing layer 120, and the linker 130.

The first through twelfth probe cells P₁-P₁₂ can be distinguished fromone another by the sequence of the probes 140 coupled to the fixinglayer 120 and/or by physical patterns of the fixing layer 120.

More specifically, probes included in the same probe cell havesubstantially the same probe sequence. On the other hand, probesincluded in different probe cells have different probe sequences.Referring to FIG. 2, all probes PROBE 5 included in the fifth probe cellP₅ have the same probe sequence. The same applies to probes PROBE 6,PROBE 7, and PROBE 8. However, when it comes to the relationship betweenthe probes PROBE5, PROBE 6, PROBE 7 and PROBE 8, the probes PROBE5,PROBE 6, PROBE 7 and PROBE 8 have different probe sequences since theyare included in different probe cells, i.e., the fifth through eighthprobe cells P₅-P₈, respectively. That is, the fifth probe cell P₅including the probes PROBE 5, the sixth probe cell P₆ including theprobes PROBE 6, the seventh probe cell P₇ including the probes PROBE 7,and the eighth probe cell P₈ including the probes PROBE 8 sequentiallyarranged from the left in FIG. 2 may be distinguished from one anotherby their probe sequences. Similarly, the same applies to the firstthrough fourth probe cells P₁-P₄ and the ninth through twelfth probecells P₉-P₁₂.

Another standard for distinguishing the first through twelfth probecells P₁-P₁₂ is a physical pattern. That is, the first through twelfthprobe cells P₁-P₁₂ may be physically patterned, and an isolation region(not shown) may be interposed between them.

As illustrated in FIG. 1, the first through twelfth probe cells P₁-P₁₂may be patterns arranged in rows and columns and have substantially thesame size and shape.

Hereinafter, a mask used for the in-situ synthesis of the probes 140 inthe microarray 100 will be described. FIG. 3 is a plan view of a mask201 according to an embodiment of the present invention. FIG. 4 is across-sectional view of the mask 201 taken along a line IV-IV′ of FIG.3.

Referring to FIG. 3, the mask 201 may be divided into a plurality ofsegments respectively corresponding to probe cells in a microarray. Eachsegment is occupied by any one of a light-transmitting region TR and alight-blocking region BR. The total number of light-transmitting regionsTR and light-blocking regions BR in the mask 201 is equal to the numberof corresponding probe cells regardless of whether the above regions areadjacent to one another. Therefore, in FIG. 3, there are twolight-transmitting regions TR and ten light-blocking regions BR.

A cross-sectional structure of the mask 201 will now be described withreference to FIG. 4. The mask 201 includes a base 220 formed oftransparent glass, a light-blocking pattern layer 230 partially formedon the base 220 and formed of an opaque material such as chrome, and areflection preventive pattern layer 240, for example, formed of chromeoxide.

The light-transmitting and light-blocking regions TR and BR of the mask201 are determined according to whether the light-blocking pattern layer230 is formed. That is, a region where the light-blocking region 230 isformed is a light-blocking region BR, and a region where thelight-blocking region 230 is not formed is a light-transmitting regionsTR since the transparent base 220 is exposed.

A method of fabricating the mask 201 will now be described withreference to FIGS. 5A through 5C. FIGS. 5A through 5C arecross-sectional views for explaining the method of fabricating the mask201 illustrated in FIG. 4.

Referring to FIG. 5A, a stack is provided of a light-blocking layer 230a, a reflection preventive layer 240 a, and a photoresist film 250 asequentially formed on the base 220. The photoresist film 250 a isselectively exposed as indicated by reference numeral 400. Here, aregion (hereinafter, referred to as an exposure region) of thephotoresist film 250 a, which is to be exposed, may be selected based ona mask layout which is prepared in advance.

Referring to FIG. 5B, the selected exposure region of the photoresistfilm 250 a is removed in a photolithography process. Consequently, aphotoresist pattern 250 exposing the reflection preventive layer 240 ais formed.

Referring to FIG. 5C, the exposed reflection preventive layer 240 a andthe light-blocking layer 230 a beneath the exposed reflection preventivelayer 240 a are etched. Consequently, the reflection preventive patternlayer 240 and the light-blocking pattern layer 230 are formed, and thesubstrate 220 thereunder is exposed. The exposed reflection preventivelayer 240 a and the light-blocking layer 230 a may be anisotropicallyetched.

Next, if the photoresist pattern 250 is removed, the mask 201illustrated in FIG. 4 can be completed. A region where the reflectionpreventive layer 240 a and the light-blocking layer 230 a therebeneathare removed is the light-transmitting region TR.

In the above fabrication process, the selective exposure process 400 ofthe photoresist film 250 a is performed using, for example, electronicbeams. In the selective exposure process 400, if the size of theselected exposure region is much smaller than the size of the mask 201,it becomes challenging to perform accurate patterning. For example, whenvarious masks are fabricated using electronic beams having the samedose, if an exposure region is excessively small, it cannot be exposedto a desired exposure dose. In addition, in a developing process, anexcessively small exposure region hinders precise development.Consequently, the reliability of mask patterns, i.e., thelight-transmitting and light-blocking regions TR and BR, is reduced.Therefore, the light-transmitting regions TR may account for anappropriate proportion of the mask patterns fabricated. For example, aproportion of the light-transmitting regions in the mask patterns may begreater than a minimum light-transmitting proportion.

The minimum light-transmitting proportion may vary according to the sizeof a light-transmitting region TR. The size of a light-transmittingregion TR is proportional to the size of a probe cell. For example, ifeach probe cell is a square having a side of about 10 μm or greater andthus an area of 100 μm² or greater, a proportion (the sum of the sizesof light-transmitting regions if there are a plurality oflight-transmitting regions) of the light-transmitting regions TR in themask 201 may be equal to or greater than approximately 5% of a totalproportion (the sum of the sizes of all light-transmitting andlight-blocking regions) of the light-transmitting and light-blockingregions TR and BR in the mask 201. However, if the size of each probecell is smaller than about 100 μm², the minimum light-transmittingproportion is greater than the above figure.

For example, if the size of each probe cell is about 1 through 100 μm²,the proportion of the light-transmitting regions TR in the mask 201 maybe equal to or greater than approximately 7.5% of the total proportionof the light-transmitting and light-blocking regions TR and BR in themask 201. If the size of each probe cell is about 0.01 through 1 μm²,the proportion of the light-transmitting regions TR in the mask 201 maybe equal to or greater than approximately 10% of the total proportion ofthe light-transmitting and light-blocking regions TR and BR in the mask201.

In FIG. 3, two of 12 segments of the mask 201 are occupied by thelight-transmitting regions TR. If the size of each light-transmittingregion TR is equal to that of each light-blocking region BR, theproportion of the light-transmitting regions TR in the mask 201 isapproximately 16.7%, that is, more than 10%, of the total proportion ofthe light-transmitting regions TR and the light-blocking regions BR inthe mask 201. Therefore, the mask 201 illustrated in FIG. 3 can beapplied when the size of each probe cell is about 0.01 μm² or greater.

FIG. 6 is a plan view of a mask 202 according to another embodiment ofthe present invention. Unlike the mask 201 illustrated in FIG. 3, themask 202 illustrated in FIG. 6 allocates one of its twelve segments to alight-transmitting region TR. Therefore, a proportion of thelight-transmitting region TR of the mask 202 illustrated in FIG. 6 isapproximately 8.3% of a total proportion of the light-transmittingregion TR and light-blocking regions BR in the mask 202. It is notimpossible to use the mask 202 to fabricate probes of a microarray inwhich the size of each probe cell is about 0.01 through 1 μm². However,the mask 202 may be used to fabricate probes of a microarray in whichthe size of each probe cell is about 1 μm² or greater to enhance thereliability of the in-situ synthesis of the probes. If the size of eachprobe cell that is to be synthesized may be within the range of about0.01 through 1 μm² and if it is challenging to change the size, thedesign pattern of the mask 202 illustrated in FIG. 6 can be changedusing a mask layout determination method according to an embodiment ofthe present invention, which will be described later, in a mask layoutprocess performed before a mask fabrication process. Hence, the mask 202may be fabricated to have the changed design pattern and providedaccordingly.

FIG. 7 is a perspective view of a mask set 21 0 according to anembodiment of the present invention. The mask set 210 includes aplurality of masks fabricated according to the above-mentionedembodiments of the present invention. Referring to FIG. 7, an exemplary,non-limiting mask set 210 according to an embodiment of the inventionincludes 12 masks M₁-M₁₂. Each of the masks M₁-M₁₂ is used for at leastone lithography process to synthesize probes of a microarray. Therefore,the mask set 210 illustrated in FIG. 7 may be used for a total of atleast 12 lithography processes to synthesize probes of a microarray. Itis to be understood, however, that this mask set is illustrative, andmask sets according to other embodiments of the invention can have adifferent number of masks.

Each lithography process is performed to synthesize a probe monomer.Therefore, each of the masks M₁-M₁₂ can be allocated to any one of aplurality of probe monomers that are to be synthesized. For example, ifa monomer that is to be synthesized is a nucleotide phosphoamiditemonomer having any one of adenine (A), guanine (G), thymine (T), andcytosine (C) as a base, each of the masks M₁-M₁₂ is allocated to thenucleotide phosphoamidite monomer having any one of adenine (A), guanine(G), thymine (T), and cytosine (C) as a base.

Each of the masks M₁-M₁₂ that comprise the mask set 210 satisfies theconditions of the masks according to the embodiments of the presentinvention. Therefore, if the mask set 210 is used to synthesize probesof a microarray having probe cells, the size of each probe cell beingabout 100 μm² or greater, the proportion of light-transmitting regionsTR in each of the masks M₁-M₁₂ may be more than approximately 5% of thetotal proportion of the light-transmitting and light-blocking regions TRand BR in each of the masks M₁-M₁₂. Similarly, if the size of each probecell is about 1 through 100 μm², the light-transmitting regions TR mayoccupy more than approximately 7.5% of each of the masks M₁-M₁₂. If thesize of each probe cell is about 0.01 through 1 μm², thelight-transmitting regions TR may occupy more than approximately 10% ofeach of the masks M₁-M₁₂.

Hereinafter, a method of fabricating a mask set according to anembodiment of the invention will be described. In the followingembodiment, for convenience, it is assumed that the size of each probecell in a microarray for probes to be synthesized is about 0.01 through1 μm² and that the proportion of light-transmitting regions in each maskis equal to or greater than approximately 10% of the total proportion ofthe light-transmitting and light-blocking regions in each mask. However,it is to be understood that methods according to other embodiments ofthe invention are not limited to probe cells of this size.

FIG. 8 is a flowchart illustrating a method of fabricating a mask setaccording to an embodiment of the present invention.

Referring to FIG. 8, a plurality of mask layouts are determined(operation S11). Here, the mask layout includes an arrangement plan ofmask patterns and mask pattern data which are required to fabricate amask. That is, the mask layout may be provided as a drawing or as a datasheet. In addition, the mask layout may be provided as a way in whichthe mask pattern data is stored in a computer.

As assumed above, all masks that are to be fabricated according to thepresent embodiment aim to have light-transmitting regions TR occupyingmore than approximately 10% of the total proportion of thelight-transmitting and light-blocking regions TR and BR. Accordingly, aplurality of mask layouts are determined to correspond to the aimedmasks.

Next, a plurality of masks are fabricated according to the determinedmask layouts (operation S12). The masks may be fabricated according tothe determined mask layouts and using a method substantially identicalto the method of fabricating a mask described above with reference toFIGS. 5A through 5C.

The operation of determining the mask layouts will now be described inmore detail.

The mask layouts may be determined using a mask layout determinationsystem. FIG. 9 is a block diagram of a mask layout determination system300 according to an embodiment of the present invention. Referring toFIG. 9, the mask layout determination system 300 includes a patterndetermination unit 310, a selection unit 320, a comparison unit 330, anda pattern change unit 340.

The pattern determination unit 310 receives probe sequence data of amicroarray, generates a plurality of mask layouts, which are applied toperforming in-situ synthesis on probes of the microarray using thereceived probe sequence data, and allocates light-transmitting regionsTR and light-blocking regions BR to each mask layout.

The selection unit 320 receives data on each mask layout to which thelight-transmitting regions TR and the light-blocking regions BR wereallocated from the pattern determination unit 310 and selects any one ofthe mask layouts.

The comparison unit 330 compares a proportion of the light-transmittingregions TR in the mask layout selected by the selection unit 320 with aminimum light-transmitting proportion. If the proportion of thelight-transmitting regions TR in the selected mask layout is equal to orgreater than the minimum light-transmitting proportion, the comparisonunit 330 transmits the comparison result to the selection unit 320.Then, the selection unit 320 selects another mask layout. If theproportion of the light-transmitting regions TR in the selected masklayout is smaller than the minimum light-transmitting proportion, thecomparison unit 330 transmits the comparison result to the patternchange unit 340.

The pattern change unit 340 exchanges light-blocking regions BR of theselected mask layout, which includes the light-transmitting regions TRoccupying a smaller proportion of the selected mask layout than theminimum light-transmitting proportion, with light-transmitting regionsTR of another unselected mask layout, thereby increasing the number oflight-transmitting regions TR included in the selected mask layout.Then, the pattern change unit 340 transmits the exchange result to thecomparison unit 330. The comparison unit 330 compares the proportion ofthe increased number of light-transmitting regions TR in the selectedmask layout with the minimum light-transmitting proportion.

Optionally, the mask layout determination system 300 may further includean examination unit 350. If the comparison unit 330 determines that theproportion of the light-transmitting regions TR in each mask layout isequal to or greater than the minimum light-transmitting proportion, theexamination unit 350 simulates probe synthesis using the mask layoutsand examines whether the sequence of the simulation-synthesized probesis substantially identical to the probe sequence data (a desired probesequence) initially provided by the pattern determination unit 310.

FIG. 10 is a flowchart illustrating a mask layout determination methodaccording to an embodiment of the present invention. Referring to FIG.10, light-transmitting regions TR and light-blocking regions BR areallocated to a plurality of mask layouts (operation S21). Specifically,any one of monomers that are to be synthesized can be allocated to eachof the mask layouts, and the sequence of the mask layouts to which anyone of monomers is allocated is determined. Next, each mask layout isdivided into a plurality of segments respectively corresponding to aplurality of probe cells. Then, the light-transmitting regions TR andthe light-blocking regions BR are allocated to each segment.

Next, it is determined whether a desired probe sequence is synthesizedin each probe cell (operation S22). If the desired probe sequence is notsynthesized, the light-transmitting regions TR and the light-blockingregions BR are allocated again to each mask layout.

If the desired probe sequence is synthesized after operations S21 andS22 are repeated, it is determined whether a proportion of thelight-transmitting regions TR in each mask layout is equal to or greaterthan a minimum light-transmitting proportion (operation S23). If theproportion of the light-transmitting regions TR in any one of the masklayouts is smaller than the minimum light-transmitting proportion,light-blocking regions BR of the selected mask layout are exchanged withlight-transmitting regions TR of another mask layout (operation S24). Inthis case, the light-transmitting and light-blocking regions TR and BR,which are exchanged with each other, may correspond to the same probecell. In addition, the same monomers may be allocated to the selectedmask layout and another mask layout, light-transmitting regions TR ofwhich are to be exchanged with light-blocking regions BR of the selectedmask layout.

Although the light-blocking regions BR are exchanged with thelight-transmitting regions TR, the same probe sequence may besynthesized in the corresponding probe cell. Probe monomers aresynthesized when they correspond to a light-transmitting region TR of amask layout which corresponds to a probe cell. In this case, themonomers that are to be synthesized may be monomers allocated to a masklayout including the light-transmitting region TR that corresponds tothe probe cell. Consequently, a probe sequence synthesized in the probecell is substantially identical to the sequence of monomers allocated tothe light-transmitting region TR that corresponds to the probe cell.Therefore, if the sequence of the monomers allocated to thelight-transmitting region TR that corresponds to the probe cell iscompared before and after the exchange, it can be identified whethersubstantially the same probe sequence is synthesized before and afterthe exchange.

After the light-blocking and light-transmitting regions BR and TR areexchanged between the mask layouts, it is determined again whether theproportion of the light-transmitting regions TR in the selected masklayout is equal to or greater than the minimum light-transmittingproportion (operation S23). If the proportion of the light-transmittingregions TR in the selected mask layout is still smaller than the minimumlight-transmitting proportion, the light-blocking and light-transmittingregions BR and TR are exchanged again (operation S24). Operations S23and S24 are repeated until the proportion of the light-transmittingregions TR in each mask layout is equal to or greater than the minimumlight-transmitting proportion. Consequently, the proportion of thelight-transmitting regions TR in each mask layout becomes equal to orgreater than the minimum light-transmitting proportion.

Optionally, it is examined whether the desired probe sequence issynthesized using the mask layouts which have exchanged thelight-transmitting and/or light-blocking regions TR and BR (operationS25). This examination is designed to enhance the reliability of themask layouts with the changed patterns. If any one pattern in aplurality of mask layouts is flawed, when probes are synthesized usingthe mask layouts, a flawed probe sequence may be synthesized, whichresults in a flaw in the entire microarray. Therefore, it is desirableto perform a probe synthesis simulation test as a last operation.

FIGS. 11 through 14 are perspective views for explaining operations ofchanging patterns of mask layouts according to an embodiment of thepresent invention. Operations S23 and S24 will now be described in moredetail with reference to FIGS. 11 through 14.

The present embodiment is based on the following non-limitingassumptions: that is, a microarray where probes are to be synthesizedincludes 12 probe cells; the size of each probe cell is within the rangeof about 0.01 through 1 μm², and a minimum light-transmitting proportionof each mask is about 10% of the proportion of light-transmitting andlight-blocking regions TR and BR in each mask; and the sequence ofmonomers to be synthesized in each probe cell is as shown in Table 1.

TABLE 1 Probe cell P₁ P₂ P₃ P₄ P₅ P₆ Probe sequence ATTC ACTA AGTC CTCTGTCT AAAG Probe cell P₇ P₈ P₉ P₁₀ P₁₁ P₁₂ Probe sequence CTGA TGTT GTAGACGT CGCG TAGT

(In Table 1, P₁-P₁₂ indicate first through twelfth probe cells. Inaddition, A, C, G and T respectively indicate monomers that are to besynthesized).

As described above with reference to FIG. 10, the patterns andarrangement of a plurality of mask layouts are determined to synthesizethe above probe sequences. A detailed description will be made withreference to Table 2 and FIG. 11.

TABLE 2 Probe Probe ML₁ ML₂ ML₃ ML₄ ML₅ ML₆ ML₇ ML₈ ML₉ ML₁₀ ML₁₁ ML₁₂Cell Sequence A C G T A C G T A C G T P₁ ATTC A T T C P₂ ACTA A C T A P₃AGTC A G T C P₄ CTCT C T C T P₅ GTCT G T C T P₆ AAAG A A A G P₇ CTGA C TG A P₈ TGTT T G T T P₉ ATAG G T A G P₁₀ ACGT A C G T P₁₁ CGCG C G C GP₁₂ TAGT T A G T Number 5 5 5 10 4 4 5 5 2 1 1 1 of light transmittingregions

Referring to Table 2 and FIG. 11, a plurality of, i.e., first throughtwelfth mask layouts ML₁-ML₁₂ are prepared and sequentially arranged.The embodiment of Table is exemplary and non-limiting, and it is to beunderstood that microarrays according to other embodiments can use adifferent number of mask layouts and a different number of probe cells.Then, monomers A, C, G and T that are to be synthesized are sequentiallyand alternately allocated to each of the first through twelfth masklayouts ML₁-ML₁₂. In addition, each of the first through twelfth masklayouts ML₁-ML₁₂ is divided into a plurality of segments respectivelycorresponding to first through twelve probe cells P₁-P₁₂. Then, monomersto be synthesized in a segment corresponding to each of the firstthrough twelfth probe cells P₁-P₁₂ in each of the first through twelfthmask layouts ML₁-ML₁₂ are checked according to the target probe sequenceof each of the first through twelfth probe cells P₁-P₁₂. Then, thelight-transmitting regions TR are allocated to the segments. Inaddition, the light-blocking regions BR are allocated to all remainingsegments except the light-transmitting regions TR of each of the firstthrough twelfth mask layouts ML₁-ML₁₂. Then, mask layouts to which thelight-transmitting regions TR are not allocated are removed, therebydetermining the final number of mask layouts. The final number of masklayouts may be determined to be a minimum applicable number.

To change the patterns of the first through twelfth mask layoutsML₁-ML₁₂, a mask layout, in which light-transmitting regions proportionis smaller than a minimum light-transmitting proportion, is selected. InTable 2, mask layouts in which the light-transmitting regions TR accountfor less than 10%, i.e., the minimum light-transmitting proportion, arethe tenth through twelfth mask layouts ML₁₀-ML₁₂. That is, each of thetenth through twelfth mask layouts ML₁₀-ML₁₂ has only onelight-transmitting region TR. Accordingly one of the tenth throughtwelfth mask layouts ML₁₀-ML₁₂ is selected. For example, the twelfthmask layout ML₁₂, which is the last one of the tenth through twelfthmask layouts ML₁₀-ML₁₂, is selected.

Next, light-blocking regions BR of the selected twelfth mask layout ML₁₂are exchanged with light-transmitting regions TR of another mask layout,that is, one of the first through eleventh mask layouts ML₁-ML₁₁. Tomaintain the probe synthesis sequence, an equal number oflight-transmitting regions TR to the number of light-blocking regionsBR, which correspond to the same probe cell, may be exchanged. In Table2, an example satisfying the above condition may be to move any one ofA, G, C, and T in a row direction to a blank column.

In addition, mask layouts, which will exchange the light-transmittingand light-blocking regions TR and BR with the selected twelfth masklayout ML₁₂, may be mask layouts which have been allocated the samemonomer as the synthesis target monomer allocated to the twelfth masklayout ML₁₂, here monomer T. That is, the fourth mask layout ML₄ and theeighth mask layout ML₈ to which the synthesis target monomer T isallocated are candidate mask layouts. A light-transmitting region TR,which can be exchanged without changing the probe sequence, is alight-transmitting region TR corresponding to fourth, fifth, and twelfthprobe cells P₄, P₅, and P₁₂ of the eighth mask layout ML₈. Therefore,one of the light-transmitting regions TR corresponding to the fourth,fifth, and twelfth probe cells P₄, P₅, and P₁₂ of the eighth mask layoutML₈ is exchanged with a corresponding light-blocking region BR of thetwelfth mask layout ML₁₂. Table 3 below shows an example in which thelight-transmitting region TR corresponding to the fourth probe cell P₄of the eighth mask layout ML₈ is exchanged with the light-blockingregion BR corresponding to the fourth probe cell P₄ of the selectedtwelfth mask layout ML₁₂. This example is also illustrated in FIG. 12.

TABLE 3 Probe Probe ML₁ ML₂ ML₃ ML₄ ML₅ ML₆ ML₇ ML₈ ML₉ ML₁₀ ML₁₁ ML₁₂Cell Sequence A C G T A C G T A C G T P₁ ATTC A T T C P₂ ACTA A C T A P₃AGTC A G T C P₄ CTCT C T C T P₅ GTCT G T C T P₆ AAAG A A A G P₇ CTGA C TG A P₈ TGTT T G T T P₉ GTAG G T A G P₁₀ ACGT A C G T P₁₁ CGCG C G C GP₁₂ TAGT T A G T Number 5 5 5 10 4 4 5 4 2 1 1 2 of light transmittingregions

It is determined whether the proportion of the light-transmitting regionTR in the selected mask layout is equal to or greater than the minimumlight-transmitting proportion. If the proportion of thelight-transmitting region TR is still smaller than the minimumlight-transmitting proportion even after the exchange of thelight-transmitting and light-blocking regions TR and BR, any one oflight-transmitting regions TR corresponding to the fifth and twelfthprobe cells P₅ and P₁₂ of the eighth mask layout ML₈ is exchanged withthe light-blocking regions BR corresponding to the same probe cells,i.e., the fifth and twelfth probe cells P₅ and P₁₂ of the twelfth masklayout ML₁₂. However, referring to Table 3 and FIG. 12, since the numberof light-transmitting regions TR of the twelfth mask layout ML₁₂ hasbeen increased to two, the proportion of the light-transmitting regionsTR is already equal to or greater than the minimum light-transmittingproportion. If the proportion of the light-transmitting regions TR isgreater than the minimum light-transmitting proportion as describedabove, the pattern change of the selected mask layout is stopped, and anext mask layout is selected. For example, the eleventh mask layout ML₁₁immediately before the twelfth mask layout ML₁₂ is selected.

Referring to Table 3 and FIG. 12, light-blocking regions BR of theselected eleventh mask layout ML₁₁ are exchanged with light-transmittingregions TR of another mask layout using the same method used to changethe pattern of the twelfth mask layout ML₁₂. In this case, it isdesirable to exclude the twelfth mask layout ML₁₂, whose pattern hasalready been changed, from candidate mask layouts. Therefore, the firstthrough tenth mask layouts ML₁-ML₁₀ can be candidate mask layouts. Ofthe first through tenth mask layouts ML₁-ML₁₀, mask layouts having beenallocated the same monomer as a synthesis target monomer allocated tothe eleventh mask layout ML₁₁, which is monomer G, are determined to befinal candidate layouts. Therefore, the third mask layout ML₃ and theseventh mask layout ML₇ to which the synthesis target monomer G isallocated are final candidate mask layouts. A light-transmitting regionTR, which can be exchanged without changing the probe sequence, is alight-transmitting region TR corresponding to the ninth and eleventhprobe cells P₉ and P₁₁ of the seventh mask layout ML₇. For example, alight-transmitting region TR corresponding to the ninth probe cell P₉ ofthe seventh mask layout ML₇ is exchanged with a light-blocking region BRcorresponding to the ninth probe cell P₉ of the eleventh mask layoutML₁₁. The result is shown in Table 4 and FIG. 13.

TABLE 4 Probe Probe ML₁ ML₂ ML₃ ML₄ ML₅ ML₆ ML₇ ML₈ ML₉ ML₁₀ ML₁₁ ML₁₂Cell Sequence A C G T A C G T A C G T P₁ ATTC A T T C P₂ ACTA A C T A P₃AGTC A G T C P₄ CTCT C T C T P₅ GTCT G T C T P₆ AAAG A A A G P₇ CTGA C TG A P₈ TGTT T G T T P₉ GTAG G T A G P₁₀ ACGT A C G T P₁₁ CGCG C G C GP₁₂ TAGT T A G T Number 5 5 5 10 4 4 4 4 2 1 2 2 of light transmittingregions

Referring to Table 4 and FIG. 13, after the light-transmitting andlight-blocking regions TR and BR are exchanged, the number oflight-transmitting regions TR of the eleventh mask layout ML₁₁ isincreased to two. Consequently, the proportion of the light-transmittingregion TR of the eleventh mask layout ML₁₁ becomes equal to or greaterthan the minimum light-transmitting proportion. Accordingly, a next masklayout is selected. Here, the remaining mask layout is the tenth masklayout ML₁₀. If the same method is used for the tenth mask layout ML₁₀,a light-transmitting region TR corresponding to the third probe cell P₃of the sixth mask layout ML₆ is a target light-transmitting region to beexchanged. If the light-transmitting region TR corresponding to thethird probe cell P₃ of the sixth mask layout ML₆ is exchanged with thelight-blocking region BR corresponding to the third probe cell P₃ of thetenth mask layout ML₁₀, the mask layout as shown in Table 5 and FIG. 14is determined.

TABLE 5 Probe Probe ML₁ ML₂ ML₃ ML₄ ML₅ ML₆ ML₇ ML₈ ML₉ ML₁₀ ML₁₁ ML₁₂Cell Sequence A C G T A C G T A C G T P₁ ATTC A T T C P₂ ACTA A C T A P₃AGTC A G T C P₄ CTCT C T C T P₅ GTCT G T C T P₆ AAAG A A A G P₇ CTGA C TG A P₈ TGTT T G T T P₉ GTAG G T A G P₁₀ ACGT A C G T P₁₁ CGCG C G C GP₁₂ TAGT T A G T Number 5 5 5 10 4 3 4 4 2 2 2 2 of light transmittingregions

Referring to Table 5 and FIG. 14, as a result of changing the patterns,the proportion of the light-transmitting regions TR in each of the firstthrough twelfth mask layouts ML₁-ML₁₂ is equal to or greater than theminimum light-transmitting proportion. Therefore, the operations ofchanging patterns are terminated, and the final patterns of the firstthrough twelfth mask layouts ML₁-ML₁₂ are determined.

Since the proportion of the light-transmitting regions TR in each of thefirst through twelfth mask layouts ML₁-ML₁₂ determined as describedabove is equal to or greater than the minimum light-transmittingproportion, if a plurality of masks are fabricated using the firstthrough twelfth mask layouts ML₁-ML₁₂, the reliability of mask patternsthat are formed can be enhanced even if an electronic beam exposure ofthe same dose is used.

A method of fabricating a microarray using a mask set according to anembodiment of the invention which includes a plurality of masks asdescribed above will now be described. FIGS. 15 through 21 areperspective views for explaining a method of fabricating a microarrayaccording to an embodiment of the present invention. For illustrativepurposes, it is assumed that a mask set used in the embodimentillustrated in FIGS. 15 through 21 has been fabricated using masklayouts determined with reference to Table 5 and FIG. 14 and that it isthe mask set illustrated in FIG. 7.

Referring to FIG. 15, a substrate 110 which includes an array of firstthrough twelfth probe cells P₁-P₁₂, and whose surface is protected by aphotolabile protecting group 150 is provided. In FIG, 15, thephotolabile protecting group 150 is connected to a linker 130 which iscoupled to the substrate 110, thereby protecting the surface of thesubstrate 110. A fixing layer is not illustrated in FIG. 15 for clarity.

Referring to FIG. 16, the probe cells on the substrate 110 are exposedusing a first mask M₁ of a mask set 210. Consequently, the first throughthird probe cells P₁-P₃, the sixth probe cell P₆, and the tenth probecell P₁₀ corresponding light-transmitting regions TR of the first maskM₁ are exposed as indicated by reference numeral 401.

Referring to FIG. 17, as a result of the exposure, the photolabileprotecting group 150 connected to the linker 130 in each of the firstthrough third probe cells P₁-P₃, the sixth probe cell P₆, and the tenthprobe cell P₁₀ is resolved, and a functional group of the linker 130 isexposed.

Referring to FIG. 18, a monomer A (141) connected to the photolabileprotecting group 150 is provided on the resultant structure of FIG. 17.The monomer A (141) connected to the photolabile protecting group 150 iscoupled to the linker 130 in each of the first through third probe cellsP₁-P₃, the sixth probe cell P₆, and the tenth probe cell P₁₀. Since thefourth probe cell P₄, the fifth probe cell P₅, and the seventh throughtwelfth probe cells P₇-P₁₂ are protected by the photolabile protectinggroup 150, the monomer A (141) connected to the photolabile protectinggroup 150 is not connected thereto. Consequently, while the monomer A(141) is synthesized in each of the first through third probe cellsP₁-P₃, the sixth probe cell P₆, and the tenth probe cell P₁₀, since itis connected to the photolabile protecting group 150, the surface of thesynthesized substrate 110 is protected again by the photolabileprotecting group 150 as illustrated in FIG. 15.

Referring to FIG. 19, the probe cells on the substrate 110 illustratedin FIG. 18 are exposed using a second mask M₂ of the mask set 210.Consequently, the second probe cell P₂, the seventh probe cell P₇, thetenth probe cell P₁₀, and the eleventh probe cell P₁₁ correspondinglight-transmitting regions TR of the second mask M₂ are exposed asindicated by reference numeral 401.

Referring to FIG. 20, as a result of the exposure, the photolabileprotecting group 150 connected to the linker 130 or the monomer A (141)in each of the second probe cell P₂, the seventh probe cell P₇, thetenth probe cell P₁₀, and the eleventh probe cell P₁₁ is resolved, and afunctional group of the linker 130 or the monomer A (141) is exposed.

Referring to FIG. 21, a monomer C (142) connected to the photolabileprotecting group 150 is provided in the resultant structure of FIG. 20.The monomer C (142) connected to the photolabile protecting group 150 iscoupled to the linker 130 or the monomer A (141), whose functional groupis exposed, in each of the second probe cell P₂, the seventh probe cellP₇, the tenth probe cell P₁₀, and the eleventh probe cell P₁₁. Since thefirst probe cell P₁, the third probe cell P₃, the fourth through sixthprobe cells P₄-P₆, the eighth probe cell P₈, the ninth probe cell P₉,and the twelfth probe cell P₁₂ are protected by the photolabileprotecting group 150, the monomer C (142) connected to the photolabileprotecting group 150 is not connected thereto. Consequently, while themonomer C (142) is synthesized in each of the second probe cell P₂, theseventh probe cell P₇, the tenth probe cell P₁₀, and the eleventh probecell P₁₁, since it is connected to the photolabile protecting group 150,the surface of the synthesized substrate 110 is protected again by thephotolabile protecting group 150 as illustrated in FIG. 15.

If the in-situ synthesis is repeated on the third through twelfth masksM₃-M₁₂ using the method described above, a microarray including thefirst through twelfth probe cells P₁-P₁₂ whose respective probesequences are as shown in Table 5 can be fabricated.

According to a mask layout determination method according to the presentinvention, a proportion of light-transmitting regions in each of aplurality of mask layouts can be controlled to be equal to or greaterthan a minimum light-transmitting proportion without changing thesequence of probes that are to be synthesized. Therefore, the patternreliability of a mask set that is fabricated can be enhanced.

While the present invention has been particularly shown and describedwith reference to exemplary embodiments thereof, it will be understoodby those of ordinary skill in the art that various changes in form anddetails may be made therein without departing from the spirit and scopeof the present invention as defined by the following claims. Theexemplary embodiments should be considered in descriptive sense only andnot for purposes of limitation.

1. A mask layout determination system comprising: a patterndetermination unit for allocating light-transmitting regions andlight-blocking regions to each of a plurality of mask layouts adapted toperforming in-situ synthesis on probes of a microarray; a selection unitfor selecting any one of the mask layouts; a comparison unit forcomparing a proportion of the light-transmitting regions in a selectedmask layout with a minimum light-transmitting proportion; and a patternchange unit for exchanging a light-blocking region of the selected masklayout with a light-transmitting region of an unselected mask layout ifthe proportion of the light-transmitting regions in the selected masklayout is smaller than the minimum light-transmitting proportion.
 2. Thesystem of claim 1, wherein the minimum light-transmitting proportion isequal to or greater than about 5% of a total proportion of thelight-transmitting and light-blocking regions.
 3. The system of claim 1,wherein the light-transmitting and light-blocking regions respectivelycorrespond to probe cells of the microarray.
 4. The system of claim 3,wherein the light-blocking region of the selected mask layout and thelight-transmitting region of the unselected mask layout, which areexchanged with each other, correspond to the same probe cell.
 5. Thesystem of claim 3, wherein the selected mask layout compared by thecomparison unit is a mask layout selected by the selection unit andhaving at least one of the light-transmitting and light-blocking regionsexchanged by the pattern change unit.
 6. The system of claim 3, furthercomprising an examination unit for examining whether a desired targetprobe is in-situ synthesized using the mask layouts which comprise themask layout whose light-blocking region is exchanged with thelight-transmitting region by the pattern change unit.
 7. A mask layoutdetermination method comprising: allocating light-transmitting regionsand light-blocking regions to each of a plurality of mask layouts whichperform in-situ synthesis on probes of a microarray; and exchanging by acomputer a light-blocking region of a mask layout with alight-transmitting region of another mask layout wherein a proportion ofthe light-transmitting regions in each mask layout is equal to orgreater than a minimum light-transmitting proportion.
 8. The method ofclaim 7, wherein the minimum light-transmitting proportion is equal toor greater than about 5% of a total proportion of the light-transmittingand light-blocking regions.
 9. The method of claim 7, wherein thelight-transmitting and light-blocking regions respectively correspond toprobe cells of the microarray.
 10. The method of claim 9, wherein thelight-blocking region of a mask layout and the light-transmitting regionof the another mask layout, which are exchanged with each other,correspond to the same probe cell.
 11. The method of claim 10, whereinany one of synthesis target monomers is allocated to each of the masklayouts, and the light-blocking and light-transmitting regions areexchanged with each other between different mask layouts to which thesame synthesis target monomer has been allocated, wherein an order ofthe synthesis target monomers allocated to the light-transmittingregions respectively corresponding to the probe cells remains unchangedbefore and after the exchange.
 12. The method of claim 9, furthercomprising examining whether a desired target probe is in-situsynthesized using the mask layouts which comprise each mask layout whoselight-blocking region is exchanged with a light-transmitting region. 13.A method of fabricating a mask set, the method comprising: allocatinglight-transmitting regions and light-blocking regions to each of aplurality of mask layouts which perform in-situ synthesis on probes of amicroarray; exchanging a light-blocking region of a mask layout with alight-transmitting region of another mask layout wherein a proportion ofthe light-transmitting regions in each mask layout is equal to orgreater than a minimum light-transmitting proportion; and fabricating aplurality of masks using the mask layouts which comprise each masklayout whose light-blocking region is exchanged with alight-transmitting region.
 14. The method of claim 13, wherein theminimum light-transmitting proportion is equal to or greater than about5% of a total proportion of the light-transmitting and light-blockingregions.
 15. The method of claim 13, wherein the light-transmitting andlight-blocking regions respectively correspond to probe cells of themicroarray.
 16. The method of claim 15, wherein the light-blockingregion of a mask layout and the light-transmitting region of the anothermask layout, which are exchanged with each other, correspond to the sameprobe cell.
 17. The method of claim 16, wherein any one of synthesistarget monomers is allocated to each of the mask layouts, and thelight-blocking and light-transmitting regions are exchanged with eachother between different mask layouts to which the same synthesis targetmonomer has been allocated, wherein an order of the synthesis targetmonomers allocated to the light-transmitting regions respectivelycorresponding to the probe cells remains unchanged before and after theexchange.
 18. The method of claim 15, further comprising examiningwhether a desired target probe is in-situ synthesized using the masklayouts which comprise each mask layout whose light-blocking region isexchanged with a light-transmitting region.